At the present time there is no specific treatment for human acute pancreatitis (AP). The objective of this project is to develop treatment modalities for this disease in an animal model. Exogenous secretin has been shown by us previously to significantly ameliorate ceruletide (CRT) induced acute pancreatitis in the rat and dog. Additionally, we have recently shown in conscious rats that concomitant infusion of the free radical scavengers superoxide dismutase (SOD) and catalase (CAT) significantly protects against AP induction by CRT. These observations suggest for the first time in an in vivo model of AP that oxygen derived free radicals play a role in the pathogenesis of the disease. A potent protease inhibitor, gabexate mesilate (FOY), has also been shown by us recently to significantly protect against induced AP. The goal of this project is to evaluate the efficacy and safety of SOD, CAT, FOY and the potent xanthine oxidase inhibitor, allopurinol, separately and in combination, with and without secretin in amelioration of established CRT induced AP in an effort to achieve specific treatments for human AP. Specific aims are to establish the efficacy, safety and optimal dose of intravenous SOD, CAT, FOY and allopurinol that might protect and ameliorate CRT induced AP in the conscious rat. We will also evaluate the efficacy of any successful agents in combination with and without secretin in ameliorating AP in this rat model. Serum enzyme levels, pancreas weight, macroscopic and microscopic changes in the pancreas will serve as markers for establishing the efficacy of the treatments. This program is clearly directed toward development of a possible mode of therapy for acute pancreatitis in an animal model. Should the hypothesis that oxygen derived free radicals play a major role in the pathogenesis of AP be correct, then interdiction of the process by SOD, CAT, allopurinol and FOY in an animal model could allow extension of this work to assessment of the role of these agents in human AP. Any form of therapy that might ameliorate the severity of this disease in humans would be a very welcome addition to our presently limited therpeutic armamentarium.